期刊
AMERICAN JOURNAL OF PATHOLOGY
卷 180, 期 3, 页码 1008-1016出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2011.11.027
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资金
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [23791785, 22591777, 21390455, 20013040]
- Grants-in-Aid for Scientific Research [20013040, 21390455, 23791785, 22591777] Funding Source: KAKEN
Monocyte chemoattractant protein-1 (MCP-1/CCL2) is reported to contribute to tumor progression and is regulated by the renin-angiotensin system in hypertensive disease. In this study, we investigated the clinical outcome of MCP-1 expression in patients with prostate cancer (CaP) and the regulation of MCP-1 through angiotensin II (AngII) type 1 receptor (AT1R) in CaP. Specimens were obtained from 138 CaP patients and analyzed by immunostaining for both MCP-1 and macrophages. We investigated the regulation of MCP-1 expression through AT1R both in vivo and in vitro using three human prostate cancer cell lines: LNCaP, C4-2, and C4-2AT6. Specimens with a high Gleason score (>= 7) and a high pathological classification (<= pT3), and those with castration-resistant prostate cancer showed significantly higher MCP-1 expression and higher macrophage infiltration than low malignant potential CaP. High MCP-1 expression in CaP correlated significantly with high prostate-specific antigen (PSA) recurrence rates. AngII induced significantly higher MCP-1 levels in C4-2AT6 than in LNCaP, whereas AT1R blockade (ARE) inhibited MCP-1 production via the inhibition of the PI3K/Akt pathway in C4-2AT6. ARB also significantly suppressed MCP-1 expression in C4-2AT6 tumors. Our study is the first to demonstrate that both high MCP-1 expression and high macrophage infiltration in CaP specimens correlate with a high PSA recurrence rate and that ARB inhibits MCP-1 expression through the PI3K/Akt pathway and blocks macrophage infiltration in castration-resistant prostate cancer. (Am J Pathol 2012, 180:1008-1016. DOI. 10.1016/j.ajpath.2011.11.027)
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